Continued advances in the field of histo pathology (and cyto pathology) over the past two decades have resulted in dramatic changes in the manner in which these disciplines are now practiced. This is especially true in the setting of a large university hospital where the role of pathologists as clinicians (diagnosticians), undergraduate and postgraduate educators, and researchers has evolved considerably. The world around us has changed significantly during this period bringing about a considerable change in our lifestyles and the way we live. This is the world of the internet and the world-wide web, the world of Google and Wikipedia, of Youtube and Facebook where anyone can obtain any information one desires at the push of a button. The practice of histo (and cyto) pathology has also evolved in line with these changes. For those practicing this discipline in a poor, developing country these changes have been breathtaking. This is an attempt to document these changes as experienced by histo (and cyto) pathologists practicing in the biggest center for Histopathology in Pakistan, a developing country in South Asia with a large (180 million) and ever growing population. The Section of Histopathology, Department of Pathology and Microbiology at the Aga Khan University Hospital (AKUH) in Karachi, Pakistan`s largest city has since its inception in the mid-1980s transformed the way histopathology is practiced in Pakistan by incorporating modern methods and rescuing histopathology in Pakistan from the primitive and outdated groove in which it was stuck for decades. It set histopathology in Pakistan firmly on the path of modernity and change which are essential for better patient management and care through accurate and complete diagnosis and more recently prognostic and predictive information as well.

Cytokine research is currently at the forefront in cancer research. Deciphering the functions of these multiple small molecules, discovered within the cell and in intercellular spaces, with their abundance and pleotrophism, was initially a great challenge. Advances in analytical chemistry and molecular biology have made it possible to unravel the pathophysiological functions of these polypeptides/proteins which are called interleukins, chemokines, monokines, lymphokines and growth factors. With more than 5 million women contracting cervical cancer every year this cancer is a major cause of mortality and morbidity the world over, particularly in the developing countries. In more than 95% of cases it is associated with human papilloma virus (HPV) infection which is persistent, particularly in those with a defective immune system. Although preventable, the mere magnitude of prevalence of HPV in the world population makes it a dominating current health hazard. The discovery of cytokine dysregulation in cervical cancer has spurted investigation into the possibility of using them as biomarkers in the early diagnosis of cases at high risk of developing cancer. Their critical role in carcinogenesis and progression of cervical cancer is now being revealed to a great extent. From diagnostics to prognosis, and now with a possible role in therapeutics and prevention of cervical cancer, the cytokines are being evaluated in all anticancer approaches. This review endeavours to capture the essence of the astonishing journey of cytokine research in cervical neoplasia.

It is becoming progressively more understandable that different phytochemicals isolated from edible plants interfere with specific stages of carcinogenesis. Cancer cells have evolved hallmark mechanisms to escape from death. Concordant with this approach, there is a disruption of spatiotemproal behaviour of signaling cascades in cancer cells, which can escape from apoptosis because of downregulation of tumor suppressor genes and over-expression of oncogenes. Genomic instability, intra-tumor heterogeneity, cellular plasticity and metastasizing potential of cancer cells all are related to molecular alterations. Data obtained through in vitro studies has convincingly revealed that curcumin, EGCG, resveratrol and quercetin are promising anticancer agents. Their efficacy has been tested in tumor xenografted mice and considerable experimental findings have stimulated researchers to further improve the bioavailability of these nutraceuticals. We partition this review into different sections with emphasis on how bioavailability of curcumin, EGCG, resveratrol and quercetin has improved using different nanotechnology approaches.

Melanoma of the skin is a malignant tumor, which incidence is still increasing. It was estimated that in the United States one person died from this cause every hour. The major risk factor of this disease is exposure to ultraviolet radiation, especially associated with the occurrence of sunburns. Patients diagnosed with distant metastases have median survival of 6-9 months. The aim of this paper was to identify the causes of delayed diagnosis of melanoma as diagnosis at an early stage seems to be the key to improve the survival rates. For this purpose, a search of medical databases such as PubMed, Google Scholar and Cancer Registers was conducted and an analysis of the literature from the years 1979-2013 was conducted.

Background: In chronic hepatitis B (CHB), the presence of hepatic steatosis (HS) seems to be associated with known host and viral factors which may influence the long-term prognosis of chronic hepatitis B (CHB), probably leading to cirrhosis and hepatocellular carcinoma (HCC). Different from chronic hepatitis C (CHC), factors associated with HS in CHB are not clearly explored. Materials and Methods: 160 CHB patients were divided into two groups depending on the results of liver biopsy. Group I consisted of 71 patients with confirmed steatosis. Group II comprised 89 patients without steatosis. The groups were compared in terms of basal characteristics, body mass index (BMI), liver enzymes (ALT, AST, ALP), serum fasting blood sugar (FBS) and lipids, hepatitis B e antigen (HBeAg), viral load, and histological findings. Results: In terms of host factors, male gender, older age, BMI, high serum FBS and lipid levels were associated with HS. On the other hand, ALT levels, the HAI scores of necroinflammation and stage of fibrosis did not associate with HS. On multivariate analysis, parameters of sex, BMI, cholesterol and FBS levels were independently associated with HS. Regarding viral factors, HBeAg negativity was significantly associated with HS (81.7%, p value 0.006), but not HBV DNA level (p value 0.520). Conclusions: HS in CHB appears to be unrelated to the status of HBV replication. However, fibrosis progression in CHB is related to variable host factors. HS may be enhanced through these factors in HBV chronic patients.

Background: This study aimed to determine nursing student knowledge, behavior and beliefs for breast cancer and breast self-examination receiving courses with a traditional lecturing method (TLM) and the Six Thinking Hats method (STHM). Materials and Methods: The population of the study included a total of 69 second year nursing students, 34 of whom received courses with traditional lecturing and 35 of whom received training with the STHM, an active learning approach. The data of the study were collected pre-training and 15 days and 3 months post-training. The data collection tools were a questionnaire form questioning socio-demographic features, and breast cancer and breast self-examination (BSE) knowledge and the Champion`s Health Belief Model Scale. The tests used in data analysis were chi-square, independent samples t-test and paired t-test. Results: The mean knowledge score following traditional lecturing method increased from to (P<0.001) and it increased from to after training with the Six Thinking Hats Method (P<0.001). It was determined that there was a significant increase in pre and post-training perceptions of perceived confidence in both groups. There was a statistically significant difference between pre-training, and 15 days and 3 months post-training frequency of BSE in the students trained according to STHM (p<0.05). On the other hand, there was a statistically significant difference between pre-training and 3 months post-training frequency of BSE in the students trained according to TLM. Conclusions: In both training groups, the knowledge of breast cancer and BSE, and the perception of confidence increased similarly. In order to raise nursing student awareness in breast cancer, either of the traditional lecturing method or the Six Thinking Hats Method can be chosen according to the suitability of the teaching material and resources.

Background: Most patients with endometrial cancer have stage I disease. Adjuvant therapy in stage IB (formerly IC) endometrial cancer is controversial, treatment options including observation or brachytherapy/radiotherapy in grade 1-3 patients with or without chemotherapy. The purpose of this study was to assess the outcomes of our patients with stage IB endometrioid endometrial cancer. Materials and Methods: Sixty two patients with stage IB endometrial cancer and endometrioid histology were retrospectively evaluated. All patients were initially treated surgically by the same surgeon with comprehensive staging, i.e. total abdominal hysterectomy, bilateral salphingooopherectomy, bilateral pelvic and paraaortic lymph node dissection and omentectomy. Adjuvant radiotherapy was discussed with patients and utilized by those who accepted. Adjuvant chemotherapy was not given to any of the patients. Results: Median age was 62 (range, 42-95). Ninety percent of the patients had grade 1-2 disease. Thirteen patients (21%) received intra vaginal brachytherapy (IVBT) and one received whole pelvic radiotherapy (WPRT). Median follow-up time was 46 months (range, 9-77 months). Three patients experienced recurrence (4.8%), two of them died on follow-up and one was still alive at last visit. Two patients with recurrence had FIGO grade 2 tumors and one had a grade 3 tumor. Two patients (3.2%) died without evidence of recurrent disease. Relapse free survival at 5 years was 94.4% and overall survival was 93.1%. Conclusions: Patients with stage IB disease in our study demonstrated relatively low recurrence rates although the majority of them received no adjuvant treatment. Surgery alone may be sufficient for most patients with this stage of endometrial cancer.

C4.4A, a metastasis-associated gene, encodes a glycolipid-anchored membrane protein which is overexpressed in several human malignancies. However, there are few data available on C4.4A expression and its relationship with progression in gastric cancer. Our study was designed to explore the expression of C4.4A in gastric cancer and to correlate it with clinical outcome. C4.4A expression was studied by quantitative real-time RT-PCR and immunohistochemistry for assessment of correlations with clinicopathological factors. C4.4A mRNA expression was significantly up-regulated in gastric cancer as compared with noncancerous tissue (p<0.05)., being observed in 107 (88.4%) of the 121 gastric cancer cases by immunohistochemistry. We found that the expression of C4.4A mRNA was correlated with size of the tumor, depth of invasion, lymph node metastasis, distant metastasis and TNM stage. Moreover, patients with overexpression of C4.4A has a significantly worse survival (p<0.05). Further multivariable analysis indicated that the expression of C4.4A was an independent prognostic indicator for gastric cancer (p<0.05). In conclusion, overexpression of C4.4A correlates with metastatic potential of gastric cancer and C4.4A could be a novel independent prognostic marker for predicting outcome.

Aim: The purpose of this study was to investigate anti-tumor effects and safety of DH332, a new -carboline alkaloids derivatives in vitro and in vivo. Materials and Methods: The effects of DH332 on human (RAMOS RA.1) and mouse (J558) B lymphoma cell lines were detected using a CCK-8 kit (Cell Counting Kit-8), and apoptosis was detected by flow cytometry with PI/annexinV staining. Western blotting was used to detected caspase-3 and caspase-8. Neurotoxic and anti-tumor effects were evaluated in animal experiments. Results: DH332 exerts a lower neurotoxicity compared with harmine. It also possesses strong antitumor effects against two B cell lymphoma cell lines with low . Moreover, DH332 could inhibit the proliferation and induce the apoptosis of RAMOS RA.1 and J558 cell lines in a dose-dependent manner. Our results suggest that DH332 triggers apoptosis by mainly activating the caspase signaling pathway. In vivo studies of tumor-bearing BALB/c mice showed that DH332 significantly inhibited growth of J558 xenograft tumors. Conclusions: DH332 exerts effective antitumor activity in vitro and in vivo, and has the potential to be a promising drug candidate for lymphoma therapy.

Background: Cytogenetic abnormalities have important implications in diagnosis and prognosis of acute leukemia and are now considered an important part of the diagnostic workup at presentation. Karyotype, if known at the time of diagnosis, guides physicians to plan appropriate management strategies for their patients. Aim and Objectives: To determine the cytogenetic profile of acute lymphoblastic leukemia (ALL) in Pakistani children in order to have insights regarding behavior of the disease. Materials and Methods: A retrospective analysis of all the cases of ALL (<15years old) diagnosed at Aga Khan University from January 2006 to June 2011 was performed. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. Results: A total of 153 patients were diagnosed as ALL during the study period, of which 127 samples successfully yielded metaphase chromosomes. The male to female ratio was 1.8:1. A normal karyotype was present in 51.2% (n

Background: To determine the potential clinical utility of tumor markers CEA, TPA, and SCC-Ag for early detection of cervical precancerous lesions. Materials and Methods: A case-control study was carried out on 120 women (46 patients with histologically confirmed cervical precancerous lesions and 74 healthy controls). The significance of serum selected tumor markers in early detection of cervical intraepithelial neoplasia (CIN) were assessed. Results: Of the case group, the rates of CIN I, II, III, was 69.6%, 23.9%, and 6.5%, respectively. According to the manufacturer`s cut-off values of 2ng/ml, 5ng/ml, and 70 U/ml for SCC-Ag, CEA and TPA tests, in that order, SCC-Ag test had a sensitivity of 13%, but CEA and TPA tests could not distinguish between case and control groups. The diagnostic sensitivities were highest at cut-off values of 0.55 ng/ml for SCC-Ag, 2.6ng/ml for CEA, and 25.5 U/ml for TPA which were 93%, 61%, and 50%, respectively. However, the area under the receiver operating characteristic curve was the largest for SCC-Ag (0.95 vs. 0.61 and 0.60 for CEA and TPA, respectively). Moreover, there was a highly significant direct correlation between SCC-Ag concentration and the degree of cervical precancerous lesions (r

Background: Hepatocellular carcinoma (HCC) is a dismal tumor with a high incidence, prevalence and poor prognosis and survival. Management of HCC necessitates multidisciplinary clinics due to the wide heterogeneity in its presentation, different therapeutic options, variable biologic behavior and background presence of chronic liver disease. We studied the different prognostic factors that affected survival of our patients to improve future HCC management and patient survival. Materials and Methods: This study is performed in a specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo University, Egypt. We retrospectively analyzed the different patient and tumor characteristics and the primary mode of management applied to our patients. Further analysis was performed using univariate and multivariate statistics. Results: During the period February 2009 till February 2013, 290 HCC patients presented to our multidisciplinary clinic. They were predominantly males and the mean age was . All cases developed HCC on top of cirrhosis that was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B (36.9%) and commonly presented with small single lesions. Transarterial chemoembolization was the most common line of treatment used (32.4%). The overall survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum bilirubin, site of the tumor and type of treatment were the significant independent prognostic factors for survival. Conclusions: Our main prognostic variables are the bilirubin level, the bilobar hepatic affection and the application of specific treatment (either curative or palliative). Multidisciplinary clinics enhance better HCC management.

RASSF1A has been reported to be a candidate tumor suppressor in esophageal squamous cell carcinoma (ESCC). However, the association between RASSF1A promoter methylation and ESCC remains unclear. Eligible studies were identified through searching PubMed, Medline, Web of Science, and the China National Knowledge Infrastucture database. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Twelve studies involving 859 cases and 675 controls were included in this meta-analysis. A significant association was observed between RASSF1A methylation and ESCC overall (OR

Background: Assessment of supportive needs is the requirement to plan any supportive care program for cancer patients. There is no evidence about supportive care needs of Iranian breast cancer patients. So, the aims of present study were to investigate this question and s predictive factors. Materials and Methods: A descriptive-correlational study was conducted, followed by logistic regression analyses. The Supportive Care Needs Survey was completed by 136 breast cancer patients residing in Iran following their initial treatment. This assessed needs in five domains: psychological, health system and information, physical and daily living, patient care and support, and sexuality. Results: Patient perceived needs were highest in the health systems and information (71%), and physical and daily living (68%) domains. Logistic regression modeling revealed that younger participants have more un-met needs in all domains and those with more children reported fewer un-met needs in patient care and support domains. In addition, married women had more un-met supportive care needs related to sexuality. Conclusions: The high rate of un-met supportive care needs in all domains suggests that supportive care services are desperately required for breast cancer patients in Iran. Moreover, services that address informational needs and physical and daily living needs ought to be the priority, with particular attention paid to younger women. Further research is clearly needed to fully understand supportive care needs in this cultural context.

Background: To elucidate the role of rapamycin and PF4 on apoptosis regulation via Bax (pro-apoptosis), Bcl-2 (anti-apoptosis) and survivin activation on the growth in the 1-methyl-1-nitrosourea-induced invasive breast carcinoma model. Materials and Methods: Thirty five female Sprague Dawley rats at age 21-day old were divided into 4 groups; Group 1 (control, n

Background: A cancer registry program has been established in East Azerbaijan and this has emphasized the importance of cancers of gastrointestinal tract in this region. The aim of the present pathology-based cancer registry report is to renew epidemiologic aspects of gastrointestinal tract cancers and estimate recent trends. Materials and Methods: A survey team reviewed and collected all records of cancer cases from all referral and valid pathology laboratories of East Azerbaijan province during September 2007-2011. Crude rates, age-specific rates of cancer incidence and annual percent change were calculated. Results: The total newly diagnosed cancer cases (n

Objective: To investigate the electronic anti-nausea instrument (EANI) combined with hydrochloride palonosetron for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Methods: Patients who received highly emetogenic chemotherapy were randomly assigned to a treatment group (60 patients) treated with EANI combined with hydrochloride palonosetron, and control group (also 60 patients) given only hydrochloride palonosetron. Chemotherapy related nausea and vomiting were observed and recorded in both groups of patients from the start till the end of chemotherapy. Results: Complete control rates of vomiting in treatment and control group were 40%, and 35%, respectively, without any statistical ly significant difference (p>0.05); however the response rates are 95.0%, 78.3%, respectively, with statistical difference (p<0.05). Complete control rates of nausea in treatment and control group were 36.7%, 30%, respectively, without statistical difference (p>0.05); but the response rates are 90.0%, 76.7%, respectively, with statistical difference (p<0.05). Conclusion: EANI combined with hydrochloride palonosetron for prevention of nausea and vomiting induced by chemotherapy could be more effective than hydrochloride palonosetron alone, and can be recommended for use in prevention and treatment of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy.

Background: The melastatin-related transient receptor potential 7 channel (TRPM7) is a nonselective cation channel that has been shown to promote tumor metastasis and progression. In this study, we determined the expression of TRPM7 in ovarian carcinomas and investigated its possible prognostic value. Materials and Methods: Samples were collected from 138 patients with ovarian cancer. Expression of TRPM7 was assessed by real-time PCR and immunohistochemistry, expressed with reference to an established scoring system and related to clinical pathological factors. Kaplan-Meier survival analysis was applied to estimate disease-free survival (DFS) and overall survival (OS). Univariate and multivariate cox regression analyses were performed to correlate TRPM7 expression levels with DFS and OS. Results: TRPM7 was highly expressed in ovarian carcinoma and significantly associated with decreased disease-free survival (DFS: median 20 months vs. 42 months, P

The tumour suppressor genes, p53 and pRb, are known to play important roles in neoplastic transformation. While molecular routes to the uncontrolled growth of hepatocytes, leading to primary liver cancer have generated considerable interest, the roles of p53 and pRb mutations in hepatocellular carcinoma (HCC) and hepatoblastoma (HB) remain to be clarified. We examined the immunohistochemical expression of p53 and pRb gene products in 26 HCC and 9 HB, sampled into tissue microarray blocks. 10 (38%) of 26 HCC showed > 10% tumour nuclear staining for p53 protein, 3 of these also being HbsAg positive. Conversely, none of 9 HB expressed nuclear p53 immunopositivity. Some 24 (92%) HCC and 8 (89%) HB showed loss of pRb nuclear expression. Two of the 26 HCC and one of the 9 HB showed >10% tumour nuclear staining for pRb protein. Our results suggest that p53 does not have an important role in the development of HB but may contribute in HCC. There is also loss of pRb expression in the majority of HCC and HB, supporting loss of pRb gene function in the hepatocarcinogenesis pathway. However, a comparison of the staining profiles of p53 and pRb proteins in HCC and HB did not reveal a consistent pattern to differentiate between the two types of tumours immunohistochemically. Hence the use of p53 and pRB protein expression has no contribution in the situation where there is a diagnostic difficulty in deciding between HCC and HB.

Background: In Iran, there are high rates of breast cancer. It is among the five most common cancers, the first among cancers diagnosed, and is the leading cause of cancer deaths among Iranian women. Objectives: The purpose of this qualitative study was to explore perception of breast cancer screening among Iranian women who have never had a mammograph. Materials and Methods: The current study was part of a qualitative research conducted by means of content analysis method and purposive sampling of 16 women over the age of 30 years who had not undergone mammography using individual semi-structured interviews. Interviews were recorded and transcribed verbatim. The data were under continuous consideration and comparative analysis in order to achieve data saturation. Results: After codification of data, three concept categories were achieved including: i) low awareness, ii) worries, and iii) lack of motivation. Conclusions: Although there is a tendency among Iranian women to participate in breast cancer screening, there is a powerful cultural belief that breasts are sexual organs that should not be discussed publicly. Due to the incidence of breast cancer in Iranian women, it is critical that breast awareness education be performed by health care experts to explore the concepts of breast cancer and breast cancer screening.

Prostate adenocarcinoma is one of the leading causes of cancer related mortality in men but still limited knowledge is available about its associated functional SNPs including rs1042522 (Pro72Arg). The present study was undertaken to explore the association of this SNP with susceptibility to prostate adenocarcinoma along with its structural and functional impacts in the Pakistani population in a case-control study. Three-dimensional structure of human TP53 with Pro72Arg polymorphism was predicted through homology modeling, refined and validated for detailed structure-based assessment. We also carried out a HuGE review of the previous available data for this polymorphism. Different genetic models were used to evaluate the genotypes association with the increased risk of PCa (Allelic contrast: OR

Ganoderma lucidum polysaccharides (GLP) extracted from Ganoderma lucidum have been shown to induce cell death in some kinds of cancer cells. This study investigated the cytotoxic and apoptotic effect of GLP on HCT-116 human colon cancer cells and the molecular mechanisms involved. Cell proliferation, cell migration, lactate dehydrogenase (LDH) levels and intracellular free calcium levels () were determined by MTT, wound-healing, LDH release and fluorescence assays, respectively. Cell apoptosis was observed by scanning and transmission electron microscopy. For the mechanism studies, caspase-8 activation, and Fas and caspase-3 expression were evaluated. Treatment of HCT-116 cells with various concentrations of GLP (0.625-5 mg/mL) resulted in a significant decrease in cell viability (P< 0.01). This study showed that the antitumor activity of GLP was related to cell migration inhibition, cell morphology changes, intracellular elevation and LDH release. Also, increase in the levels of caspase-8 activity was involved in GLP-induced apoptosis. Western blotting indicated that Fas and caspase-3 protein expression was up-regulated after exposure to GLP. This investigation demonstrated for the first time that GLP shows prominent anticancer activities against the HCT-116 human colon cancer cell line through triggering intracellular calcium release and the death receptor pathway.

Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma longa L. has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms by which it induces apoptosis is limited. In this study, the anticancer efficacy of curcumin was investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that curcumin induced morphological changes and decreased cell viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7-AAD staining. Curcumin-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (MMP) and the release of cytochrome c into the cytosol. Furthermore, the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3 and increased cleaved PARP was observed in SGC-7901 cells treated with curcumin. Therefore, curcumin-induced apoptosis of SGC-7901 cells might be mediated through the mitochondria pathway, which gives the rationale for in vivo studies on the utilization of curcumin as a potential cancer therapeutic compound.

Background: Diabetes is a chronic disease characterized by impaired fasting blood glucose that leads to disturbances in various organs. In this study, we evaluated relationships between tumor size and grade in a population of diabetic and non-diabetic patients with renal cell carcinoma. Materials and Methods: Between 2007-2013, in our clinic radical nephrectomy performed to 310 patients for renal tumors and pathology reported renal cell carcinoma cases were enrolled in the study. Patients with and without a history of diabetes regarding fasting glucose and HgA1c levels were evaluated during surgery for tumor size and Fuhrman grade. Results: Diabetes was found in 95 patients. The mean age of the patients with and without diabetes mellitus was 64.3 (40-79) and 58.4 (31-87) years, respectively. In the diabetes group 51% of patients had a tumor size over 7 cm and 54% a tumor grade over Fuhrman 3. The respective figures in the non-diabetes group were 35% and 30% (p<0.05 in both cases). Conclusions: Renal cancer appears more aggressive in patients with diabetes. In this study lifestyle and risk factors with diabetes regulation were observed to be important for renal cancer patients. Multicenter studies are needed in larger series for more accurate results.

Background: Infection with certain human papillomavirus (HPV) genotypes is the most important risk factor related with cervical cancer. The objective of the present study was to investigate the prevalence of HPV infection, the distribution of HPV genotypes and HPV E6/E7 oncogene mRNA expression in Turkish women with different cervical cytological findings in Mersin province, Southern Turkey. Materials and Methods: A total of 476 cytological samples belonging to women with normal and abnormal cervical Pap smears were enrolled in the study. For the detection and genotyping assay, a PCR/direct cycle sequencing approach was used. E6/E7 mRNA expression of HPV-16, 18, 31, 33, and 45 was determined by type-specific real-time NASBA assay (NucliSENS EasyQHPV v1.1). Results: Of the 476 samples, 106 (22.3%) were found to be positive for HPV DNA by PCR. The presence of HPV was significantly more common (p<0.001) in HSIL (6/8, 75%) when compared with LSIL (6/14, 42.9%), ASC-US (22/74, 29.7%) and normal cytology (72/380, 18.9%). The most prevalent genotypes were, in descending order of frequency, HPV genotype 66 (22.6%), 16 (20.8%), 6 (14.2%), 31 (11.3%), 53 (5.7%), and 83 (4.7%). HPV E6/E7 oncogene mRNA positivity (12/476, 2.5%) was lower than DNA positivity (38/476, 7.9%). Conclusions: Our data present a wide distribution of HPV genotypes in the analyzed population. HPV genotypes 66, 16, 6, 31, 53 and 83 were the predominant types and most of them were potential carcinogenic types. Because of the differences between HPV E6/E7 mRNA and DNA positivity, further studies are required to test the role of mRNA testing in the triage of women with abnormal cervical cytology or follow up of HPV DNA positive and cytology negative. These epidemiological data will be important to determine the future impact of vaccination on HPV infected women in our region.

Background: This study investigated the utilization of both problem and emotion focused coping strategies and their association with aspects of quality of life among Turkish women with ovarian cancer undergoing chemotherapy. Materials and Methods: The convenience sample consisted of 228 patients in all disease stages. The data were collected using the brief COPE, QOL-Cancer patient tool, sociodemographic sheet, and medical variables were gathered from patients` medical charts. Results: Findings reveal that quality of life is moderately high for this group of cancer patients, despite some specific negative facets of the illness and treatment experience. Acceptance, emotional support and religion were the most frequently used problem-focused coping strategies and self-distraction, venting and behavioral disengagement were the most frequently used emotion-focused coping strategies reported by patients. Overall quality of life and, particularly, psychological and spiritual well-being scores of younger patients were lower. Patients reported using significantly more problem-focused coping than emotion-focused coping, and more problem-focused and less emotion-focused coping predicted greater quality of life. Problem-focused coping was related to patients` physical and spiritual well-being and emotion-focused coping was related inversely with psychological and social well-being. Conclusions: Coping strategies are influential in patient quality of life and their psychosocial adaptation to ovarian cancer. Psycho-oncology support programs are needed to help patients to frequent use of problem-focused coping and reduce emotion-focused coping strategies to improve overall quality of life.

Because of its importance in tumor invasion and metastasis, the epithelial-mesenchymal transition (EMT) has become a research focus in the field of cancer. Recently, evidence has been presented that FoxO4 might be involved in EMT. Our study aimed to detect the expression of FoxO4, E-cadherin and vimentin in non-small cell lung cancers (NSCLCs). We also investigated clinical features and their correlations with the markers. In our study, FoxO4, E-cadherin and vimentin were assessed by immunohistochemistry in a tissue microarray (TMA) containing 150 cases of NSCLC. In addition, the expression level of FoxO4 protein was determined by Western blotting. The percentages of FoxO4, E-cadherin and vimentin positive expression in NSCLCs were 42.7%, 38.7% and 55.3%, respectively. Immunoreactivity of FoxO4 was low in NSCLC when compared with paired normal lung tissues. There were significant correlations between FoxO4 and TNM stage (P<0.001), histological differentiation (P

Metformin has been shown to be useful in reducing insulin resistance by restoring sensitivity. Recent evidence suggests that metformin might also possess anti-tumour activity. This study aimed to investigate the effects of cisplatin combined with metformin on the proliferation, invasion and migration of HNE1/DDP human nasopharyngeal carcinoma (NPC) cells, and to provide a new target for treating metastasis. The MTT assay was used to assess viability of HNE1/DDP cells after exposure to different concentrations of 2, 5-diaminopyrimidine-4, 6-diol (DDP; 2, 4, 8, 16, and ), metformin (5, 10, 15, 20, and ), and of DDP combined with metformin. Wound healing and transwell migration assays were performed to assess cell migration and invasion, and expression of E-cadherin and MMP-9 was detected using Western blotting. MTT assay results showed that DDP could inhibit the proliferation of HNE1/DDP cells in a time- and concentration-dependent manner, with an IC50 of at 24 h (P < 0.05), whereas low concentrations of DDP had almost no inhibitory effects on cell invasion and migration. DDP combined with metformin significantly inhibited cell invasion and migration. In addition, genes related to migration and invasion, such as those of E-cadherin and MMP-9, showed differential expression in the NPC cell line HNE1/DDP. In the present study, with an increasing concentration of metformin, the expression of MMP-9 was downregulated whereas that of E-cadherin was significantly upregulated. Taken together, our results show that cisplatin combined with metformin has effects on proliferation, invasion, and migration of human NPC cells.

Background: Relationships between smoking and bladder neoplasms, one of the common malignancies, are well-known. Different smoking-related malignancies may occur together. In this study, we evaluated the stage and grade of bladder neoplasms in patients also featuring lung or larynx cancer. Materials and Methods: From January 2006 to February 2012, patients who underwent surgery for bladder neoplasms in our clinic were screened retrospectively. In the evaluation, 5 patients had larynx cancer and 20 patients have lung cancer in addition, all having been smoking for a long time. The bladder tumor stage and grade were investigated in these 25 cases. Results: Mean age of patients was 66.8 (49-78). In the evaulation, all of 5 patients who had larnyx cancer also had high grade urothelial cancer. One had T2 urothelial, and 3 T1 urothelial cancer. In the same way, all of the 20 patients with lung cancer also have high grade urothelial cancer, three T2, and 13 T1. Bladder cancer stage and grade were determined to be significantly increased in patients with concomitant bladder and lung or larynx cancer. Conclusions: In the patients who have smoking releated second malignancy, bladder cancer prognosis appears more aggressive. We now need a larger series and multi-center studies for understanding relevant pathophysiology.

Purpose: The aim of this study was to analyze any association between the metabolic syndrome (MetS) and risk of prostate cancer (PCa) and cancer grade among men undergoing radical prostatectomy for PCa. Materials and Methods: 50 patients with MetS and 50 patients without MetS who undervent radical prostatectomy (RP) were included in the study. Age at biopsy, height, weight, digital rectal examination (DRE), pre-biopsy PSA levels, prostate volume, histopathologic diagnosis after surgery and gleason scores were collected data from all patients. Histologic material obtained at biopsy was given a Gleason score; tumours with a Gleason score were considered high grade and <7 were considered low grade. Results: The mean age at the time of biopsy was in patients with MetS and in patients without MetS. Men with MetS had significantly lower PSA levels (p

Emerging evidence has shown associations of microRNA-205 (miR-205) with crucial cell processes such as the epithelial-mesenchymal transition (EMT) and aberrant expression with tumorigenesis in many types of human malignancy. This prospective study characterized the contribution of miR-205 to the colorectal cancer (CRC) tumorigenesis. The real-time reverse transcription-polymerase chain reaction was used to examine miR-205 levels prospectively in 36 pairs of samples of CRC tissue and adjacent noncancerous tissue (>2 cm from cancer tissue). In addition, the relationship between miR-205 levels and clinicopathological features was explored. The capability of miR-205 to function as a tumor marker was also examined. miR-205 expression levels did not show significant changes overall. However, miR-205 was significantly downregulated in a group of CRC samples compared with matched noncancerous tissue samples. Moreover, decreased miR-205 correlated significantly with lymphatic metastasis. A receiver operating characteristic (ROC) curve also showed an optimum cut off point of to distinguish lymphatic metastatic CRCs from non-metastatic CRCs. Interestingly we found lymphatic metastasis in almost 80% of the depressed samples. This study suggested that miR-205 could be reduced in the majority of metastatic CRCs and the risk of CRC metastasis may be predicted by monitoring miR-205 in patient samples collected at the time of the initial diagnosis. Therefore, targeting miR-205 and its potential environmental activators might be a promising therapeutic option to prevent malignant progression toward metastasis.

Background: The aim of this study was to investigate the anti-cancer effects and mechanisms of immunochemotherapy of 5-fluorouracil (5-FU) and interleukin-2 (IL-2) on non-small cell lung cancer (NSCLC) A549 cells. Materials and Methods: In order to detect whether 5-FU+IL-2 could effectively inhibit tumor growth in vivo, we established an A549-bearing nude mouse model. The cytotoxicity of natural killer (NK) cells was evaluated using a standard chromium release assay. To evaluate the relevance of NK cells in 5-FU+IL-2-mediated tumor inhibitory effects, we depleted NK cells in A549-bearing mice by injecting anti-asialo-GM-1 antibodies. Effects of 5-FU+IL-2 on the expression and promoter activity of NKG2D ligands (MICA/MICB) in A549 cells in vitro were also assessed. Results: In A549-bearing nude mice, combination therapy significantly inhibited tumor growth in comparison with monotherapy with 5-FU or IL-2 and enhanced the recognition and lysis of tumor cells by NK cells. Further study of mechanisms showed that NK cells played a vital role in the anticancer immune response of 5-FU+IL-2 immunochemotherapy. In addition, the combination therapy synergistically stimulated the expression and promoter activity of MICA/MICB. Conclusions: 5-FU and IL-2 immunochemotherapy significantly inhibited tumor growth and activated NK cytotoxicity in vivo, and these effects were partly impaired after depleting NK cells in tumor-bearing mice. Combination treatment of 5-FU and IL-2 upregulated the expression and the promoter activity of MICA/MICB in A549 cells, which enhanced the recognition of A549 cells by NK cells. All of the data indicated that immunochemotherapy of 5-FU and IL-2 may provide a new treatment option for patients with lung cancer.

Effects of transforming growth factor-beta (TGF-) were investigated in human colorectal cancer, and the influence of cantharidinate in inhibiting TGF- expression was explored. Relationships among TGF- and sex, age, tumor size, tumor location, tumor stage were also analyzed. H&E and immunohistochemistry staining were employed to assess colorectal cancer and TGF- expression, respectively. Then, HCT-116 CRC cells were randomly divided into four groups, controls, no serum-treated, chemotherapy and cantharidinate-treated. Immunohistochemistry and real-time PCR were employed to assess the expression of TGF- in CRC cells. Our data showed that the expression of TGF- might be associated with tumor size and tumor location (P<0.05). The expression of TGF- in CRC groups was higher than in adjacent groups (P<0.05). In addition, the expression of TGF- in cantharidinate-treated group was much lower than in CRC group (P<0.05). Taken together, these results suggest that TGF- plays an important role in CRC development. Cantharidinate might inhibit the expression of TGF- and control the development of colorectal cancer.

Background: Race and ethnicity are significant factors in predicting survival time of breast cancer patients. In this study, we applied advanced statistical methods to predict the survival of White non-Hispanic female breast cancer patients, who were diagnosed between the years 1973 and 2009 in the United States (U.S.). Materials and Methods: Demographic data from the Surveillance Epidemiology and End Results (SEER) database were used for the purpose of this study. Nine states were randomly selected from 12 U.S. cancer registries. A stratified random sampling method was used to select 2,000 female breast cancer patients from these nine states. We compared four types of advanced statistical probability models to identify the best-fit model for the White non-Hispanic female breast cancer survival data. Three model building criterion were used to measure and compare goodness of fit of the models. These include Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC). In addition, we used a novel Bayesian method and the Markov Chain Monte Carlo technique to determine the posterior density function of the parameters. After evaluating the model parameters, we selected the model having the lowest DIC value. Using this Bayesian method, we derived the predictive survival density for future survival time and its related inferences. Results: The analytical sample of White non-Hispanic women included 2,000 breast cancer cases from the SEER database (1973-2009). The majority of cases were married (55.2%), the mean age of diagnosis was 63.61 years (SD

Background: To evaluate whether ABO-Rh blood groups have significance in the treatment response and prognosis in patients with non-metastatic breast cancer. Materials and Methods: We retrospectively evaluated files of 335 patients with breast cancer who were treated between 2005 and 2010. Demographic data, clinic-pathological findings, treatments employed, treatment response, and overall and disease-free survivals were reviewed. Relationships between clinic-pathological findings and blood groups were evaluated. Results: 329 women and 6 men were included to the study. Mean age at diagnosis was 55.2 years (range: 26-86). Of the cases, 95% received chemotherapy while 70% were given radiotherapy and 60.9% adjuvant hormone therapy after surgery. Some 63.0% were A blood group, 17.6% O, 14.3% B and 5.1% AB. In addition, 82.0% of the cases were Rh-positive. Mean follow-up was 24.5 months. Median overall and progression-free survival times were 83.9 and 79.5 months, respectively. Overall and disease-free survival times were found to be higher in patients with A and O blood groups (p<0.05). However rates did not differ with the Rh-positive group (p

The presence of viral DNA in breast cancer cells is controversial. However, some studies have revealed a possible role for the human papillomavirus in the pathogenesis of breast cancer. The aim of the present study was to investigate the presence of HPV-DNA in breast tissue in a group of Iranian women with and without breast cancer and identification of the detected HPV types. Paraffin-embedded specimens from 65 malignant breast cancer cases and 65 cases with benign breast lesions were investigated for presence of HPV-DNA by nested polymerase chain reaction. We found HPV-DNA in 22 (33.8%) of the breast cancer specimens. All non-cancerous specimens were negative. Low and high-risk HPV types, including HPV-6 (26.2%), HPV-16 (1.5%), HPV-35 (1.5%), HPV-52 (1.5%), and HPV-11 (1.5%) were detected in our study. HPV-6 was the most prevalent type in the breast cancer specimens. Although high-risk HPV types have been shown to have a major role in cervix cancer, there have been no data that support the same relevance for other types of malignancies. Furthermore, presence of low-risk HPV types in malignancies still is a matter of debate. The data presented in this study indicates a strong need for epidemiological studies correlating different HPV types in human breast cancer.

Background: The Chinese Hui ethnic group has diverse origins, including Arab, Persian, Central Asian, and Mongol. The standardized mortality rate of gastric cancer in the Hui population is higher than the overall Chinese population. In this study, we investigated whether COX-2-765G>C polymorphism, an extensively studied polymorphism, contributes to gastric cancer and its precursor lesions (GPL) in the Chinese Hui ethnic group. Materials and Methods: COX-2-765G>C polymorphism was determined by pyrosequencing in 100 gastric cancer cases, 102 gastric cancerand its precursor lesions cases and 105 controls. Data were statistically analyzed using Chi-square tests and logistic regression models. Results: Among the Chinese Hui ethnic group COX-2-765 C allele carriers were at increased risk for gastric cancer (OR

Background: The effects of CYP1A1 gene polymorphisms on the risk of bladder cancer (BC) remain controversial. We carried out a meta-analysis to clarify the role of CYP1A1 gene polymorphisms in BC. Material and Methods: A comprehensive literature search was conducted up to November 20, 2013. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the association. Meta-regression, subgroup analysis, sensitivity analysis and publication bias were also performed. Results: Eight studies involving 1,059 BC cases and 1,061 controls were included. The meta-analysis showed that there was no significant association between the two common mutations of CYP1A1 and BC risk. For the I1e462Val A/G polymorphism with GG vs. AA the OR was 1.47 (95 % CI

Background: Previous studies have showed that argonaute 2 is a potential factor related to genesis of several cancers, however, there have been no reports concerning gliomas. Methods: Paraffin specimens of 129 brain glioma cases were collected from a hospital affiliated to Binzhou Medical University from January 2008 to July 2013. We examined both argonaute 2 mRNA and protein expression by real-time quantitative PCR (qRT-PCR), Western blot analysis, and immunohistochemistry (IHC). The survival curves of the patients were determined using the Kaplan-Meier method and Cox regression, and the log-rank test was used for statistical evaluations. Results: Both argonaute 2 mRNA and protein were upregulated in high-grade when compared to low-grade tumor tissues. Multivariate analysis revealed that argonaute 2 protein expression was independently associated with the overall survival (HR

Background: Atelectasis is an important prognostic factor that can cause pleuritic chest pain, coughing or dyspnea, and even may be a cause of death. In this study, we aimed to investigate the potential impact of atelectasis and PET parameters on survival and the relation between atelectasis and PET parameters. Materials and Methods: The study consisted of patients with lung cancer with or without atelectasis who underwent -FDG PET/CT examination before receiving any treatment. -FDG PET/CT derived parameters including tumor size, SUVmax, SUVmean, MTV, total lesion glycosis (TLG), SUV mean of atelectasis area, atelectasis volume, and histological and TNM stage were considered as potential prognostic factors for overall survival. Results: Fifty consecutive lung cancer patients (22 patients with atelectasis and 28 patients without atelectasis, median age of 65 years) were evaluated in the present study. There was no relationship between tumor size and presence or absence of atelectasis, nor between presence/absence of atelectasis and TLG of primary tumors. The overall one-year survival rate was 83% and median survival was 20 months (n

Background: This study used the receiver operating characteristic curve (ROC) to analyze Surveillance, Epidemiology and End Results (SEER) bronchioaveolar carcinoma data to identify predictive models and potential disparity in outcomes. Materials and Methods: Socio-economic, staging and treatment factors were assessed. For the risk modeling, each factor was fitted by a Generalized Linear Model to predict cause specific survival. The area under the ROC was computed. Similar strata were combined to construct the most parsimonious models. A random sampling algorithm was used to estimate modeling errors. Risk of cause specific death was computed for the predictors for comparison. Results: There were 7,309 patients included in this study. The mean follow up time (S.D.) was 24.2 (20) months. Female patients outnumbered male ones 3:2. The mean (S.D.) age was 70.1 (10.6) years. Stage was the most predictive factor of outcome (ROC area of 0.76). After optimization, several strata were fused, with a comparable ROC area of 0.75. There was a 4% additional risk of death associated with lower county family income, African American race, rural residency and lower than 25% county college graduate. Radiotherapy had not been used in 2/3 of patients with stage III disease. Conclusions: There are socio-economic disparities in cause specific survival. Under-use of radiotherapy may have contributed to poor outcome. Improving education, access and rates of radiotherapy use may improve outcome.

The X-ray repair cross-complementing group 1 protein (XRCC1) plays important roles in the DNA base excision repair pathway which may influence the development of lung cancer. This study aimed to evaluate the potential association of the XRCC1 c.1178G>A genetic polymorphism with lung cancer risk. The created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods were utilized to evaluate the XRCC1 c.1178G>A genetic polymorphism among 376 lung cancer patients and 379 controls. Associations between the genetic polymorphism and lung cancer risk were determined with an unconditional logistic regression model. Our data suggested that the distribution of allele and genotype in lung cancer patients was significantly different from that of controls. The XRCC1 c.1178G>A genetic polymorphism was associated with an increased risk of lung cancer (AA vs GG: OR

Protein phosphatase 1 (PP1) is a major serine/threonine phosphatase that controls gene expression and cell cycle progression. The active mutant IPP5 (), the latest member of the inhibitory molecules for PP1, has been shown to inhibit the growth of human cervix carcinoma cells (HeLa). In order to elucidate the underlying mechanisms, the present study assessed overexpression of in HeLa cells. Flow cytometric and biochemical analyses showed that overexpression of induced G2/M-phase arrest, which was accompanied by the upregulation of cyclin B1 and phosphorylation of G2/M-phase proteins ATM, p53, and Cdc2, suggesting that induces G2/M arrest through activation of the ATM/p53//Cdc2/cyclin B1 pathways. We further showed that overexpression of led to delayed nuclear translocation of cyclin B1. also could translocate to the nucleus in G2/M phase and interact with and Cdc2 as demonstrated by co-precipitation assay. Taken together, our data demonstrate a novel role for in regulation of cell cycle in HeLa cells, possibly contributing to the development of new therapeutic strategies for cervix carcinoma.

Background: Accurate assessment of disease progression requires proper understanding of natural disease process which is often hidden and unobservable. For this purpose, disease status should be clearly detected. But in most diseases it is not possible to detect such status. This study, therefore, aims to present a model which both investigates the unobservable disease process and considers the error probability in diagnosis of disease states. Materials and Methods: Data from 330 patients with gastric cancer undergoing surgery at the Iran Cancer Institute from 1995 to 1999 were analyzed. Moreover, to estimate and assess the effect of demographic, diagnostic and clinical factors as well as medical and post-surgical variables on transition rates and the probability of misdiagnosis of relapse, a hidden Markov multi-state model was employed. Results: Classification errors of patients in alive state without a relapse () and with a relapse () were 0.22 (95% CI: 0.04-0.63) and 0.02 (95% CI: 0.00-0.09), respectively. Only variables of age and number of renewed treatments affected misdiagnosis of relapse. In addition, patient age and distant metastasis were among factors affecting the occurrence of relapse (state1state2) while the number of renewed treatments and the type and extent of surgery had a significant effect on death hazard without relapse (state2state3)and death hazard with relapse (state2state3). Conclusions: A hidden Markov multi-state model provides the possibility of estimating classification error between different states of disease. Moreover, based on this model, factors affecting the probability of this error can be identified and researchers can be helped with understanding the mechanisms of classification error.